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Acta Tropica 151 (2015) 1620

Contents lists available at ScienceDirect

Acta Tropica
journal homepage: www.elsevier.com/locate/actatropica

The importance of the multidisciplinary approach to deal with the


new epidemiological scenario of Chagas disease (global health)
Maria-Jesus Pinazo , Joaquim Gascon
Instituto de Salud Global de Barcelona, Hospital Clnic, Universitat de Barcelona, Rosell, 1344 , 08036 Barcelona, Spain

a r t i c l e

i n f o

Article history:
Received 8 April 2015
Received in revised form 11 June 2015
Accepted 15 June 2015
Available online 15 July 2015
Keywords:
Chagas disease
Trypanosoma cruzi
Triatoma infestans
Migration
Oral transmission
Benznidazole

a b s t r a c t
There are currently two major factors that have modied the epidemiology of Chagas disease in the last
decades: climate change and migration ows. In this new scenario, there are new challenges to control
and prevent Trypanosoma cruzi infection in endemic countries, such as the control of a wider distribution
of triatomine vectors or the reinforcement of vertical transmission programs. In non-endemic areas,
few countries are aware of the emergence of this new disease and have established changes in their
health systems. To address this new public health challenge, the priorities should be control programs to
avoid new cases of T. cruzi infection acquired through vertical transmission, blood transfusion or organ
transplant.
In both, endemic and non-endemic areas, the international community and all the actors involved in
Chagas disease must join efforts mainly in two directions: better management of the infection in affected
individuals and more research to cover the knowledge gap mainly in physiopathology, diagnosis and
treatment.
2015 Elsevier B.V. All rights reserved.

1. Introduction: the keys of disease globalization in the XXI


century
Chagas disease, caused by Trypanosoma cruzi parasite, was originally described as an endemic disease focused in populations living
in poor rural areas of Latin American countries.
From the ecological point of view, there have been two major
factors that have modied the epidemiology of the disease: climate
change and human migration. Even if it is difcult to quantify the
impact of climate change in vector borne disease transmission, altitude levels of the traditionally dened endemic areas, the wild cycle
of triatomine and the vector-parasite interaction can be modied
due to global warming (Asin and Catal, 1995; Carcavallo, 1999).
Moreover, anthropical factor, through various initiatives of vector control, add an important element to the epidemiological issue
in endemic countries.
Historically, migration has been the key factor in the dissemination of Chagas disease (Guhl et al., 1999). Recently, migrant ows
have brought infected individuals to Latin American urban areas
and beyond the borders of Latin America, changing the epidemiology of the disease (Gascon et al., 2010).

Corresponding author.
E-mail addresses: mariajesus.pinazo@isglobal.org (M.-J. Pinazo),
jgascon@clinic.ub.es (J. Gascon).
http://dx.doi.org/10.1016/j.actatropica.2015.06.013
0001-706X/ 2015 Elsevier B.V. All rights reserved.

The migratory ows between Latin American and European


countries are not new. During the fteenth century many European
citizens migrated towards the Americas. This process continued
until the fties of the twentieth century, when Latin America
became a region of origin of international migrants, being the
United States and Europe the main receptors of Latin America
migrants. This trend has continued until 2008, when due to the economic crisis the migratory ows from LA, signicantly decreased.
United States is the main destination of Latin American migration
with approximately 20.5 million Latin American immigrants living
in the country, according to some estimates (CEPAL, 2006). Today,
around 3.5 million people from Latin American live in Europe
(Jackson et al., 2014). In Europe, the distribution by country of
Lain American migrants follows a patchy pattern, where certain
few countries concentrate most of the Latin American migration.
Spain, with over half of these migrants, is undoubtedly the most
important recipient, followed by Italy, France, and United Kingdom
(Requena-Mendez et al., 2015).
This initial distribution is changing due to the economic crisis
and currently there is a redistribution of Latin American migration,
especially from Spain to other European countries (Jackson et al.,
2014).
One of the features that affect many Latin American immigrants
today is the fact that the migration process does not stop with a single shift; quite often migrants look for job opportunities in three
or more countries in relatively short periods of time. These fre-

M.-J. Pinazo, J. Gascon / Acta Tropica 151 (2015) 1620

quent changes involve European and American countries, posing a


challenge to the health care of these people.
2. New characteristics of Chagas disease in endemic
countries
T. cruzi (T. cruzi) infection is a complex entity caused by a heterogeneous species of the parasite T. cruzi that implies a wide
diversity of animals in the wild cycle, playing domestic animals
an important epidemiological role in some areas (Gurtler et al.,
2007). The distribution of Chagas disease in endemic areas has been
described as patchy and heterogeneous, involving different ecological niches and more than one hundred triatominae species, the
vector of the disease (Noireau et al., 2009). Five triatomine vectors
species (Triatoma infestans, Rhodnius prolixus, Triatoma dimidiata,
Panstrongylus megistus, and T. brasiliensis) have a major epidemiological importance (Patterson and Guhl, 2010), and it seems that
there is a close association between some triatomine vector species
and some specic strains of T. cruzi (Gaunt and Miles, 2000; Yeo
et al., 2005).
The transmission of T. cruzi in humans can occur in in
well-known ways, and several approaches of control have been
developed.
2.1. Vector transmission and programs of vector control
The implementation of vector control programs started in the
90s through several initiatives along the endemic countries has
contributed to change dramatically the epidemiology of Chagas
disease in Latin America (Dias et al., 2002; Guhl, 2007). The goal
in most of these programs was the interruption of the domestic
and peridomestic cycles of transmission through insecticide spraying. These programs only useful for domiciliary vectors have
been successful in several countries: Brazil, Uruguay, and Chile have
been declared free from disease transmission by T. infestans, as well
as specic departments of several other countries (Moncayo and
Silveira, 2009; Guhl et al., 2009). Equally, Guatemala was certied
as being free from disease transmission by R. prolixus, the main
domiciliated vector for Chagas disease in Central America (Guhl
et al., 2009). But the temporal action of insecticides is not permanent. As demonstrated by some authors, recolonisation of houses
by sylvatic triatomine populations may explain some difculties
encountered in vector control (Fitzpatrick et al., 2008).
Triatomine re-infestation is one of the major challenges in
endemic areas, which oblige to maintain active the vector control programs. The decentralization of vector control is still
controversial, although it is one of the keys for a sustainable entomological surveillance. Selective control and surveillance strategies
are required due to the risk of possible domiciliary re-infestations
(Guhl et al., 2009).
Moreover, there are reports showing the emergence of insecticide resistance among triatominos (Gurevitz et al., 2012; Lardeux
et al., 2010).
2.2. Rural to urban migration
In endemic countries, and mainly due to economic reasons,
people living in rural areas moved to urban areas, increasing urbanization in periurban areas with poor hygienic conditions and where
T. cruzi transmission can persist (Medrano-Mercado et al., 2008).
2.3. Increasing detection of T. cruzi infection cases transmitted by
oral transmission
Human oral infection is caused by ingestion of drinks or food
contaminated with infected triatomine bugs or their feces. It has

17

been rarely described up to now, but in the last years there has
been an increase of new cases and outbreaks reported, mainly in
wild environments (Roellig et al., 2009) but also in urban areas. Several cases and outbreaks have been reported in Brazil, Venezuela,
Colombia, Mexico, Argentina, and Bolivia (Alarcon de Noya et al.,
2010; Shikanai-Yasuda et al., 1991; da Silva Valente et al., 1999;
Coura, 1997; Vargas et al., 2011).
2.4. Vertical transmission: the lack of surveillance programs
Vertical transmission of Chagas disease is one the main challenges of health in endemic countries (Alonso-Vega et al., 2013;
Martins-Melo et al., 2014), and it is not well managed yet. Due
to the success of the programs of vector and blood bank control,
congenital transmission has obtained increasing epidemiological
importance (Gurtler et al., 2003). Rates of congenital T. cruzi transmission range from less than 1% to 28.6% (Howard et al., 2014),
and the WHO estimated number of new cases of congenital T. cruzi
infection is around 8.668 cases per year (WHO, 2015).
2.5. Successful blood banks control in Latin America countries
Specic screening for T. cruzi in blood banks has been improved
successfully in all Latin-American countries in the last years, with
a coverage close to 100% (Schmunis, 2007; Dias, 2007).
3. Chagas as emerging disease in non-endemic countries
As mentioned before, in non-endemic countries, new migration
ows have been the key for the emergence of Chagas disease in
areas where it was not previously present. The importance of Chagas disease in this new scenario is directly related to the volume
of migration ows received by each host country and also related
to the specic origin of migrants received, since the distribution of
Chagas disease is not homogeneous within endemic countries.
Europe and the United States have been the main recipients of
Latin-American migration (Guhl et al., 1999; Dias, 2007), and due
to the current economic crisis some trends of migrant dispersion
among European countries have been detected.
It is estimated that in Europe there are between 68.000 and
123.000 infected people with T. cruzi, most of them living in Spain.
However, until 2009 only 4.290 cases have been reported (Gascon
et al., 2010; Basile et al., 2011).
In the United States, based on population gures from countries where Chagas disease is endemic, it is estimated that in 2011
there were about 300.000 people infected with T. cruzi (Bern and
Montgomery, 2009).
In other countries with Latin American migration (Canada,
Japan, Australia, other European countries) the number of people
infected by T. cruzi ranges from 140 (Austria) to over 12,000 (England) (Gascon et al., 2010; Basile et al., 2011; Guerri-Guttenberg
et al., 2008).
In non-endemic countries T. cruzi transmission occurs through
blood transfusion and organ transplants from infected donors and
from infected mothers to their children as well.
3.1. Blood banks control strategies in non-endemic countries
Few studies have been conducted in blood banks in nonendemic countries to assess the risk of transmission in blood banks.
In Spain, one study showed that 0.62% of the Latin American donors
(N = 1172) were positive for Chagas disease, but the percentage
increased (10%) when only Bolivian migrants were considered
(Piron et al., 2008). In other studies between 1% and 5% of blood
donors were detected to be positive for Chagas disease in the U.S.,

18

M.-J. Pinazo, J. Gascon / Acta Tropica 151 (2015) 1620

Canada and Germany (Kirchhoff et al., 1987; Frank et al., 1997;


Steele et al., 2007).
Additionally, several cases of Chagas disease transmission in
blood and transplants recipients have been reported in Europe
and the United States (Villalba et al., 1992; Perez de Pedro and
Santamaria, 2008; Cimo et al., 1993; Fores et al., 2007; Leiby et al.,
1999; Young et al., 2007). In Spain, universal blood donation screening for T. cruzi began in 2005 and in the U.S. in 2007. In Europe
only four more countries (France, Switzerland, United Kingdom,
and Sweden) have implemented effective measures to control risk
of Chagas disease infection via blood transfusion (Bern et al., 2008;
Ministerio de Salud y Consumo, 2005; Requena-Mndez et al.,
2014).
3.2. A new route of transmission: organ transplantation
Organ transplantation is more frequent in non-endemic than in
endemic countries, and the new era of organ transplantation has
opened another route of transmission of the parasite. The management of this clinical condition is especially important while
immunosuppression is mandatory in the context of organ transplant. Several guidelines in endemic and non-endemic countries
have been published for this new scenario (Pinazo et al., 2011;
Ministerio de Salud de la Nacin, 2012; Dias and Coura, 1997).
3.3. Non-endemic countries becoming endemic countries:
vertical transmission
The risk of mother-to-child transmission is of concern in nonendemic countries. In a study performed in Spain, the rate of
prevalence of T. cruzi in Latin American pregnant women (N = 1350)
was 3.4% (27% in Bolivian mothers), with 7.3% of infected newborns
(Munoz et al., 2009).
In Europe and the United States, respectively, it is estimated
that each year between 20 and 183, and 63115 of newborns are
infected with T. cruzi (Dias, 2007; Bern and Montgomery, 2009). In
fact, several cases of vertical transmission have already been identied in Europe (Munoz et al., 2009; Riera et al., 2006; Munoz et al.,
2007; Jackson et al., 2009; Oliveira et al., 2010; Pehrson et al., 1981;
Barona-Vilar et al., 2012).
In Spain, a study showed that doing a screening in pregnant
women for early detection and treatment to children infected by T.
cruzi was cost-effective (Sicuri et al., 2011).
Following epidemiological and economic data, some regions
of European countries, particularly Catalonia, Valencia, Galicia
and more recently Andaluca (Spain) and Tuscany (Italy) have
already approved ofcial control measures in pregnant women at
risk of T. cruzi infection and the early control of newborns from
Chagas positive mothers (Departament de Salut. Generalitat de
Catalunya, 2010; Conselleria de Sanitat. GeneralitataValenciana,
2009; SEDUTA, 2012).
Also in Europe, there are some other punctual initiatives from
some centers for the control of newborns whose mothers are
infected with T. cruzi (Requena-Mndez et al., 2014). Due to the high
efcacy of specic T. cruzi treatment in newborns (of nearly 100%),
programs for the control of Chagas disease via congenital transmission should be implemented in all countries to screen pregnant
women coming from endemic areas with the objective of early
treating the infected newborns.
4. Challenges on Chagas disease management in this new
global scenario
Despite being globalized, Chagas disease remains one of the 17
neglected tropical diseases declared by the World Health Organization. Chagas disease has a signicant economic impact. The global

costs for Chagas disease have been estimated in $7.19 billion per
year, similar or even higher to those of other important diseases
(Lee et al., 2013).
Vector control programs and oral transmission of Chagas disease are specic challenges for endemic countries, although due
to human migration the repercussion of the success or failure of
such programs goes beyond the Americas. Although endemic countries have direct responsibility for maintaining appropriate vector
control programs, strengthening such programs is a major global
challenge in which international community should be involved.
Other challenges on Chagas disease are universal, mainly to
improve control programs of vertical transmission in endemic
areas, and to develop such programs in non-endemic countries.
Endemic and many of the newly affected countries are registering cases of the disease transmitted congenitally. However, few
countries are aware of the emergence of this new disease and few
have established changes in their health system to address this new
challenge for public health (Requena-Mndez et al., 2014). Despite
the clinical, economic and epidemiological data available, effective vertical transmission control programs are not in place both in
most endemic and non-endemic countries (Requena-Mndez et al.,
2014).
As a neglected disease, there are several gaps in the knowledge
of crucial points in Chagas disease: the life cycle of T. cruzi in human
hosts, the ecology of sylvatic cycle, the mechanisms of action of
drugs against the parasite and the keys to improve the accessibility
of the patients to the health systems. Funding for Chagas disease
in 2012 was 31.7 US$ million, which represents around 1% of total
R&D funding spent on neglected diseases globally (G-Finder survey,
2013).
In this scenario, care of people with Chagas disease has been
hampered by several factors. Here, we want to highlight some of
them: the adverse events caused by the only two useful drugs
against T. cruzi, the lack of early biomarkers of therapeutic efcacy
and, above all, the importance given to the autoimmune theory of
the disease that has prevailed for many years. For years, health professionals have been trained in the belief that Chagas disease had
no treatment and in the fear of giving the specic treatment due to
the high rates of adverse events. Other consequences of the lack of
medical care are that patients carry the social stigma and negative
psychological and economic effects of having an incurable disease.
The economic effects and the complexity of medical care are
most evident in the more advanced stages of the disease (pacemakers, debrillators, colon surgery. . .), and in these cases is not
always possible to give the required care, either by economic or
geographical reasons.
Moreover, research for new and better drugs have been slowed
or forgotten for years until very recently (Viotti et al., 2014).
In non-endemic countries, there are other important factors
relating to the care of people affected. One of them is the lack of
knowledge about the disease of many health professionals. This is
aggravated by the change of migration patterns within or between
countries when migrants are forced to move in search of better job
opportunities and also for the wide diversity and poor specicity of
symptoms of Chagas disease. Another problem relates to the policies of some governments to restrict the access of immigrants to
health systems (Jackson et al., 2014).
In order to overcome these limitations in patients treatment,
it is important to consider that: (a) adverse events of antiparasitic
drugs against T. cruzi are frequent. Even most of them are minor,
a considerable percentage of treated patients suffer from adverse
events and there is a need for monitoring patients closely during
the treatment (Viotti et al., 2009; Pinazo et al., 2010 Pinazo et al.,
2010); (b) antiparasitic treatment provided to young women prevent further cases of congenital Chagas disease (Fabbro et al., 2014);
(c) benznidazole induce a persistent negativization of the periph-

M.-J. Pinazo, J. Gascon / Acta Tropica 151 (2015) 1620

eral parasitemia in around 80% of treated patients 12 months after


treatment (Urbina, 2015; Torrico, 2013; Molina et al., 2014); (d)
even if evidences with good clinical outcomes are lacking, there is
a clinical benet in treating patients (Viotti et al., 2006); (e) the
training of health professionals is vital for good patient care; (f) to
integrate the care of patients with Chagas disease into the primary
health programs is probably the most effective strategy in both,
endemic and non-endemic countries.
5. Conclusions
The conuence of a disease inuenced by changes in ecology
and epidemiology, with a long asymptomatic phase, not clearly
perceived as being related to infection, and affecting marginalized
populations, has resulted in a silent public health crisis (Gascon
et al., 2014).
For facing this challenging disease, the international community
and all the actors that play a role against Chagas disease must join
efforts. There are precedents, such as the success of vector control
programs, which indicate that when various actors come together
to arrange a common and clear goal, this can be achieved (Schoeld
et al., 2006).
In fact, a multidisciplinary approach is essential to address a
health problem that is multifaceted, which includes the coordination of various control programs (vector, vertical, blood banks,
transplant), and the attention to affected people (primary care,
different specialists). Moreover, the decision makers must decide
priorities within their competence in face of other health problems
and coordinate with professionals working in the eld and with the
people affected.
In 2012, a community of international partners endorsed the
London Declaration on Neglected Tropical Diseases (NTDs) (World
Health Organization, 2012). This initiative, which calls to coordinate efforts to eliminate or control 10 NTDs, including Chagas
disease, drew a new scenario of possibilities until 2020. However,
few years after the initiative it seems that little have been done and
that the dened goals need to be revised (Tarleton et al., 2014).
Acknowledgements
ISGLOBAL Research group receives funds from the Agncia de
Gesti dAjuts Universitaris i de Recerca (AGAUR) grant number
2014SGR26, and from the Tropical Disease Cooperative Research
Network (RICET), grant number RD12/0018/0010.
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